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https://read.qxmd.com/read/30769924/systematic-degradation-rate-analysis-of-surface-functionalized-porous-silicon-nanoparticles
#1
Rae Hyung Kang, Seo Hyeon Lee, Sangrim Kang, Jinyoung Kang, Junho K Hur, Dokyoung Kim
Porous silicon nanoparticles (pSiNPs) have been utilized within a wide spectrum of biological studies, as well as in chemistry, chemical biology, and biomedical fields. Recently, pSiNPs have been constantly coming under the spotlight, mostly in biomedical applications, due to their advantages, such as controlled-release drug delivery in vivo by hydrolysis-induced degradation, self-reporting property through long life-time photoluminescence, high loading efficiency of substrate into pore, and the homing to specific cells/organ/bacteria by surface functionalization...
February 15, 2019: Materials
https://read.qxmd.com/read/30744931/anti-cholinesterase-hybrids-as-multi-target-directed-ligands-against-alzheimer-s-disease-1998-2018
#2
REVIEW
Pankaj Mishra, Amit Kumar, Gautam Panda
Alzheimer's disease (AD) is a genetically complex, progressive and irreversible neurodegenerative disorder of the brain which involves multiple associated etiological targets. The complex pathogenesis of AD gave rise to multi-target-directed ligands (MTDLs) principle to combat this dreaded disease. Within this approach, the design and synthesis of hybrids prevailed greatly because of their capability to simultaneously target the intertwined pathogenesis components of the disease. The hybrids include pharmacophoric hybridization of two or more established chemical scaffolds endowed with the desired pharmacological properties into a single moiety...
January 25, 2019: Bioorganic & Medicinal Chemistry
https://read.qxmd.com/read/30742682/testing-of-library-preparation-methods-for-transcriptome-sequencing-of-real-life-glioblastoma-and-brain-tissue-specimens-a-comparative-study-with-special-focus-on-long-non-coding-rnas
#3
Marek Vecera, Jiri Sana, Jan Oppelt, Boris Tichy, Kopkova Alena, Radim Lipina, Martin Smrcka, Radim Jancalek, Marketa Hermanova, Leos Kren, Ondrej Slaby
Current progress in the field of next-generation transcriptome sequencing have contributed significantly to the study of various malignancies including glioblastoma multiforme (GBM). Differential sequencing of transcriptomes of patients and non-tumor controls has a potential to reveal novel transcripts with significant role in GBM. One such candidate group of molecules are long non-coding RNAs (lncRNAs) which have been proved to be involved in processes such as carcinogenesis, epigenetic modifications and resistance to various therapeutic approaches...
2019: PloS One
https://read.qxmd.com/read/30738082/functionalized-phenylbenzamides-inhibit-aquaporin-4-reducing-cerebral-edema-and-improving-outcome-in-two-models-of-cns-injury
#4
George W Farr, Christopher H Hall, Susan M Farr, Ramon Wade, Joshua M Detzel, Amielia G Adams, Jasen M Buch, Derek L Beahm, Christopher A Flask, Kui Xu, Joseph C LaManna, Paul R McGuirk, Walter F Boron, Marc F Pelletier
Cerebral edema in ischemic stroke can lead to increased intracranial pressure, reduced cerebral blood flow and neuronal death. Unfortunately, current therapies for cerebral edema are either ineffective or highly invasive. During the development of cytotoxic and subsequent ionic cerebral edema water enters the brain by moving across an intact blood brain barrier and through aquaporin-4 (AQP4) at astrocyte endfeet. Using AQP4-expressing cells, we screened small molecule libraries for inhibitors that reduce AQP4-mediated water permeability...
February 6, 2019: Neuroscience
https://read.qxmd.com/read/30717384/subclinical-lipopolysaccharide-from-salmonella-enteritidis-induces-dysregulation-of-bioactive-substances-from-selected-brain-sections-and-glands-of-neuroendocrine-axes
#5
Anita Mikołajczyk, Dagmara Złotkowska
Bacterial lipopolysaccharide (LPS) can contribute to the pathogenesis and the clinical symptoms of many diseases such as cancer, mental disorders, neurodegenerative as well as metabolic diseases. The asymptomatic carrier state of Salmonella spp. is a very important public health problem. A subclinical single dose of LPS obtained from S. Enteritidis (5 μg/kg, i.v.) was administered to discern the consequences of changes of various brain peptides such as corticotropin-releasing hormone (CRH), gonadotropin-releasing hormone (GnRH), thyrotropin-releasing hormone (TRH), galanin (GAL), neuropeptide Y (NPY), somatostatin (SOM), substance P (SP), and vasoactive intestinal polypeptide (VIP) in selected clinically important brain sections and endocrine glands of the hypothalamic-pituitary-adrenal (HPA), -thyroid (HPT), -ovarian (HPO) axes...
February 2, 2019: Toxins
https://read.qxmd.com/read/30702848/global-portrait-of-protein-targets-of-metabolites-of-the-neurotoxic-compound-bia-10-2474
#6
Zhen Huang, Daisuke Ogasawara, Uthpala I Seneviratne, Armand B Cognetta, Christopher W Am Ende, Deane M Nason, Kimberly Lapham, John Litchfield, Douglas S Johnson, Benjamin F Cravatt
Clinical investigation of the fatty acid amide hydrolase (FAAH) inhibitor BIA 10-2474 resulted in serious adverse neurological events. Structurally unrelated FAAH inhibitors tested in humans have not presented safety concerns, suggesting that BIA 10-2474 has off-target activities. A recent activity-based protein profiling (ABPP) study revealed that BIA 10-2474 and one of its major metabolites inhibit multiple members of the serine hydrolase class to which FAAH belongs. Here, we extend these studies by performing a proteome-wide analysis of covalent targets of BIA 10-2474 metabolites...
January 31, 2019: ACS Chemical Biology
https://read.qxmd.com/read/30663099/new-99m-tc-co-3-radiolabeld-arylpiperazine-pharmacophore-as-potent-5-ht-1a-serotonin-receptor-radiotracer-docking-studies-chemical-synthesis-radiolabeling-and-biological-evaluation
#7
Mostafa Erfani, Hadi Malek, Seyed Esmaeil Sadat Ebrahimi, Leila Hassanzadeh
In spite of previous efforts there is lack of a radiotracer for imaging the 5HT1A receptor density in human brain which is involved in several neurological brain disorders. The aim of this study was to prepare a new derivative of 1-(2-methoxyphenyl) piperazine (MPP) as a main chemical structure of 5HT1A receptor antagonist with 3-carbons linker and radio-labeled by [99m Tc][Tc (CO)3 (H2 O)3 ]+ precursor. Docking studies before chemical synthesis, showed similar fashion of interaction for both WAY100635 (potent 5HT1A receptor antagonist) and new designed ligand, despite of addition of 99m Tc-(CO)3 group in the structure of new ligand...
January 20, 2019: Journal of Labelled Compounds & Radiopharmaceuticals
https://read.qxmd.com/read/30659885/methylmercury-s-chemistry-from-the-environment-to-the-mammalian-brain
#8
REVIEW
Pablo A Nogara, Cláudia S Oliveira, Gabriela L Schmitz, Paulo C Piquini, Marcelo Farina, Michael Aschner, João B T Rocha
Methylmercury is a neurotoxicant that is found in fish and rice. MeHg's toxicity is mediated by blockage of -SH and -SeH groups of proteins. However, the identification of MeHg's targets is elusive. Here we focus on the chemistry of MeHg in the abiotic and biotic environment. The toxicological chemistry of MeHg is complex in metazoans, but at the atomic level it can be explained by exchange reactions of MeHg bound to -S(e)H with another free -S(e)H group (R1 S(e)-HgMe + R2 -S(e)H ↔ R1 S(e)H + R2 -S(e)-HgMe)...
January 16, 2019: Biochimica et biophysica acta. General subjects
https://read.qxmd.com/read/30657477/aptamer-superstructure-based-electrochemical-biosensor-for-sensitive-detection-of-atp-in-rat-brain-with-in-vivo-microdialysis
#9
Yanan Jiang, Wenjie Ma, Wenliang Ji, Huan Wei, Lanqun Mao
Highly sensitive and selective sensing of ATP in rat brain has attracted increasing interest from interdisciplinary fields of analytical chemistry and neuroscience owing to the importance of ATP in cellular metabolism and signal transduction. Herein, we demonstrated an electrochemical biosensor having an aptamer superstructure as a recognition element for the selective and sensitive detection of ATP in rat brain. Unlike the electrochemical aptamer-based sensors (aptasensors) built by assembling a simple DNA structure containing only one aptamer unit onto the electrode substrate, the aptasensor described here was developed by assembling an aptamer superstructure consisting of consecutive aptamer units in DNA strands onto the electrode substrate...
January 18, 2019: Analyst
https://read.qxmd.com/read/30648158/minimally-invasive-microelectrode-biosensors-based-on-platinized-carbon-fibers-for-in-vivo-brain-monitoring
#10
Charles Chatard, Andrei Sabac, Laura Moreno-Velasquez, Anne Meiller, Stephane Marinesco
The ability to monitor the chemical composition of brain interstitial fluid remains an important challenge in the field of bioanalytical chemistry. In particular, microelectrode biosensors are a promising resource for the detection of neurochemicals in interstitial fluid in both animals and humans. These biosensors can provide second-by-second temporal resolution and enzymatic recognition of virtually any redox or nonredox molecule. However, despite miniaturization of these sensors to 50-250 μm in diameter to avoid vascular and cellular injury, inflammation and foreign-body reactions still occur following their implantation...
December 26, 2018: ACS Central Science
https://read.qxmd.com/read/30644073/oligonucleotide-therapeutics-as-a-new-class-of-drugs-for-malignant-brain-tumors-targeting-mrnas-regulatory-rnas-mutations-combinations-and-beyond
#11
REVIEW
Anna M Krichevsky, Erik J Uhlmann
Malignant brain tumors are rapidly progressive and often fatal owing to resistance to therapies and based on their complex biology, heterogeneity, and isolation from systemic circulation. Glioblastoma is the most common and most aggressive primary brain tumor, has high mortality, and affects both children and adults. Despite significant advances in understanding the pathology, multiple clinical trials employing various treatment strategies have failed. With much expanded knowledge of the GBM genome, epigenome, and transcriptome, the field of neuro-oncology is getting closer to achieve breakthrough-targeted molecular therapies...
January 14, 2019: Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics
https://read.qxmd.com/read/30630705/a-longitudinal-magnetic-resonance-spectroscopy-study-investigating-effects-of-risperidone-in-the-anterior-cingulate-cortex-and-hippocampus-in-schizophrenia
#12
Nina V Kraguljac, Charity J Morgan, Meredith A Reid, David M White, Ripu D Jindal, Soumya Sivaraman, Bridgette K Martinak, Adrienne C Lahti
Magnetic Resonance Spectroscopy is a popular approach to probe brain chemistry in schizophrenia (SZ), but no consensus exists as to the extent of alterations. This may be attributable to differential effects of populations studied, brain regions examined, or antipsychotic medication effects. Here, we measured neurometabolites in the anterior cingulate cortex (ACC) and hippocampus, two structurally dissimilar brain regions implicated in the SZ pathophysiology. We enrolled 61 SZ with the goal to scan them before and after six weeks of treatment with risperidone...
January 7, 2019: Schizophrenia Research
https://read.qxmd.com/read/30621291/preparation-of-messenger-rna-nanomicelles-via-non-cytotoxic-peg-polyamine-nanocomplex-for-intracerebroventicular-delivery-a-proof-of-concept-study-in-mouse-models
#13
Long Yi Chan, Yit Lung Khung, Chin-Yu Lin
The specific delivery of messenger RNA (mRNA) is an excellent alternative to plasmid DNA, due to the latter's potential risk for random integration into the host genome. In this study, we propose the use of specially tailored polyplex nanomicelles for the intravenous delivery of mRNA into the brain of mice. In brief, along the backbone of a polyaspartamide polymer that is terminated with a 42k Polyethylene glycol chain (PEG), aminoethylene-repeating groups (two, three, and four units, respectively) were conjugated to side-chains to promote electrostatic interactions with mRNA...
January 5, 2019: Nanomaterials
https://read.qxmd.com/read/30607820/vernonia-amygdalina-del-stimulated-glucose-uptake-in-brain-tissues-enhances-antioxidative-activities-and-modulates-functional-chemistry-and-dysregulated-metabolic-pathways
#14
Ochuko L Erukainure, Olajumoke A Oyebode, Collins U Ibeji, Neil A Koorbanally, Md Shahidul Islam
Brain glucose uptake is usually reduced in type 2 diabetes owing to downregulation of brain glucose transporters. The ability of Vernonia amygdalina to stimulate glucose uptake as well as ameliorate glucose-induced oxidative stress and proinflammation were investigated in rat brain. Hot infusion of V. amygdalina leaves was incubated with rat brain tissues for 2 h in the presence of glucose. Another incubation with glucose only, served as negative control while metformin served as positive control. Incubation of brain tissues with V...
January 3, 2019: Metabolic Brain Disease
https://read.qxmd.com/read/30594783/an-overview-of-tramadol-and-its-usage-in-pain-management-and-future-perspective
#15
REVIEW
Muna Subedi, Shalini Bajaj, Maushmi S Kumar, Mayur Yc
Patients with chronic non-malignant pain report impairment of physical and social life along with psychological state affecting their overall quality of life. The purpose of managing pain is to reduce the trauma and improve the patient comfort with better quality of life. Tramadol is a centrally acting weak μ-opioid receptor analgesic and is a racemic mixture of (+)-tramadol and (-)-tramadol enantiomers. Tramadol is used worldwide and is listed in many medical guidelines for pain management. The (+)-tramadol has greater affinity for μ-opioid receptor and provides additional prevention of 5- hydroxy tryptamine reuptake, while the (-)-tramadol is a successful noradrenaline reuptake inhibitor and intensifies its release by activating the auto receptor...
December 27, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://read.qxmd.com/read/30568753/towards-identifying-potent-new-hits-for-glioblastoma
#16
Chris Sherer, Saurabh Prabhu, David Adams, Joseph Hayes, Farzana Rowther, Ibrahim Tolaymat, Tracy Warr, Timothy J Snape
Glioblastoma is a devastating disease of the brain and is the most common malignant primary brain tumour in adults. The prognosis for patients is very poor with median time of survival after diagnosis measured in months, due in part to the tumours being highly aggressive and often resistant to chemotherapies. Alongside the ongoing research to identify key factors involved in tumour progression in glioblastoma, medicinal chemistry approaches must also be used in order to rapidly establish new and better treatments for brain tumour patients...
November 1, 2018: MedChemComm
https://read.qxmd.com/read/30542281/study-of-the-tissue-distribution-of-tlqp-21-in-mice-using-18-f-jmv5763-a-radiolabeled-analog-prepared-via-18-f-aluminum-fluoride-chelation-chemistry
#17
Elia A Turolla, Silvia Valtorta, Elena Bresciani, Jean-Alain Fehrentz, Liliana Giuliano, Stefano Stucchi, Sara Belloli, Paolo Rainone, Francesco Sudati, Laura Rizzi, Laura Molteni, Pascal Verdiè, Jean Martinez, Antonio Torsello, Rosa Maria Moresco, Sergio Todde
TLQP-21 is a neuropeptide that is involved in the control of several physiological functions, including energy homeostasis. Since TLQP-21 could oppose the early phase of diet-induced obesity, it has raised a huge interest, but very little is known about its mechanisms of action on peripheral tissues. Our aim was to investigate TLQP-21 distribution in brain and peripheral tissues after systemic administration using positron emission tomography. We report here the radiolabeling of NODA-methyl phenylacetic acid (MPAA) functionalized JMV5763, a short analog of TLQP-21, with [18 F]aluminum fluoride...
2018: Frontiers in Pharmacology
https://read.qxmd.com/read/30540906/orphan-receptor-gpr88-as-an-emerging-neurotherapeutic-target
#18
Na Ye, Bang Li, Qi Mao, Eric A Wold, Sheng Tian, John A Allen, Jia Zhou
While G protein-coupled receptors (GPCRs) are recognized as pivotal drug targets involved in multiple physiological and pathological processes, the majority of GPCRs including orphan GPCRs (oGPCRs) are unexploited. GPR88, a brain-specific oGPCR with particularly robust expression in the striatum, regulates diverse brain and behavioral functions including cognition, mood, movement control and reward-based learning, and is thus emerging as a novel drug target for CNS disorders including schizophrenia, Parkinson's disease, anxiety and addiction...
December 12, 2018: ACS Chemical Neuroscience
https://read.qxmd.com/read/30530190/polycyclic-maleimide-based-derivatives-as-first-dual-modulators-of-neuronal-calcium-channels-and-gsk-3%C3%AE-for-alzheimer-s-disease-treatment
#19
Alessandra Bisi, Raquel L Arribas, Matteo Micucci, Roberta Budriesi, Alessandra Feoli, Sabrina Castellano, Federica Belluti, Silvia Gobbi, Cristobal de Los Rios, Angela Rampa
Current healthcare has significantly increased the average life expectancy, leading to a consequently greater incidence of age-related diseases, such as Alzheimer's disease. Following a multitarget approach, in this paper a series of polycyclic maleimide-based derivatives were designed and synthesized aimed at simultaneously modulate neuronal calcium channels and glycogen synthase kinase 3-beta (GSK-3β), validated targets to combat Alzheimer' disease. Different structural modifications were performed on the polycyclic scaffold in order to investigate the structure-activity relationships and compound 10 emerged as a promising non-toxic lead compound, endowed with calcium modulating brain-addressed properties and significant GSK-3β inhibitory activity...
December 3, 2018: European Journal of Medicinal Chemistry
https://read.qxmd.com/read/30516229/the-biological-fate-of-gadolinium-based-mri-contrast-agents-a-call-to-action-for-bioinorganic-chemists
#20
Mariane Le Fur, Peter Caravan
Gadolinium-based contrast agents (GBCAs) are widely used with clinical magnetic resonance imaging (MRI), and 10 s of millions of doses of GBCAs are administered annually worldwide. GBCAs are hydrophilic, thermodynamically stable and kinetically inert gadolinium chelates. In clinical MRI, 5-10 millimoles of Gd ion is administered intravenously and the GBCA is rapidly eliminated intact primarily through the kidneys into the urine. It is now well-established that the Gd3+ ion, in some form(s), is partially retained in vivo...
December 5, 2018: Metallomics: Integrated Biometal Science
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